Fungicidal compositions and methods



3,322,618 FUNGICEDAL COMPQQTIQNS AND METHQDS Harold M. Taylor, Indianapolis, lind., assignor to Eli Lilly and Company, lndianapolis, Ind, a corporation of Indiana No Drawing. Filed Apr. 16, 1963, Sci. No. 273,282 11 Claims. (Cl. 167-30) This invention relates to novel fungicidal compositions and to fungicidal processes employing these compositions. More especially, this invention concerns novel fungicidal compositions in which a substituted aminoalkyl ester of a halogen-substituted benzoic acid is the fungicidally active ingredient.

The compounds of the present invention have been found useful in controlling both fungi which attack food crops and fungi which damage ornamental plants.

The susceptible fungi which attack food crops include Phyzophthora infesrans, the causative organism of tomato and potato late blight; Uromyces plmseoli, the causative organism of bean rust; Colletotrichum lagenarz'um, the causative organism of cucumber anthracnose; Erysz'phe polygoni, the causative organism of bean powdery mildew; Venturia inaequalis, the causative organism of apple scab; and Erysiphe cichoracearum, the causative organism of cantaloupe powdery mildew.

The susceptible fungi which affect ornamental plants include Sphaerothcca pannosa var. rosae, the causative organism of powdery mildew of rose; Microsphaera alni var. vaccinii, the causative organism of powdery mildew of catalpa; Erysiphe cichoracearum, the causative organism of Zinnia powdery mildew; Cercospora zirmiae, the causative organism of Cercospora leafspot of Zinnia; and Microsphaera alm', the causative organism of powdery mildew of lilac.

It is an object of this invention to provide compositions which are toxic to certain fungi affecting food crops and ornamental plants. A further object is to provide novel compositions and processes which serve to control such fungi.

In fulfillment of the above and other objects, this invention provides a novel process which comprises applying to plant foliage a fungicidal amount of one or more alkylaminoalkyl esters of a halogen-substituted benzoic acid of the class represented by the following formula:

wherein R and R are halogen; R and R when taken separately, are C -C alkyl or C C alkenyl; R and R when taken together with the nitrogen atom to which they are attached, represent morpholino, C -C polymethyleneimino, or lower-alkyl substituted C -C polymethyleneimino; and Z is C C saturated alkylene, C C unsaturated alkylene, C -C3 oxaalkylene, or C -C thiaalkylene. Also included within the scope of this invention are the acid addition salts of the bases represented by the above formula.

Halogen in the above formula can be fluorine, bromine, chlorine, iodine, or astatine.

The alkyl radicals in the above formula can be illustratively methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.- butyl, iso-butyl, n-amyl, iso-amyl, sec.-amyl, n-hexyl, sec.- hexyl, iso-hexyl, n-heptyl, iso-heptyl, sec.-heptyl, n-octyl, iso-octyl, sec.-octyl, and the like. The alkenyl groups can be illustratively vinyl, l-propenyl, 2-propenyl, Z-methyl- 2-propenyl, l-butenyl, Z-butenyl, Z-methyl-Z-butenyl, 3- butenyl, and the like.

The polymethyleneimino radical can be illustratively l-pyrrolidyl, Z-methyl-l-pyrrolidyl, B-methyl-l-pyrrolidyl,

3,32Zfil8 Patented May 3Q, 1967 Fire 2,3-dimethyl-l-pyrrolidyl, 2,4-dimethyl-1-pyrrolidyl, 2,5- dimethyl-l-pyrrolidyl, 3,4-dimethyl-l-pyrrolidyl, l-piperidyl, Z-methyl-l-piperidyl, 3-methyl-l-piperidyl, 4-methyl- 1-piperidyl, 2,2-dirnethyl-l-piperidyl, 2,6-dimethyl-l-piperidyl, 2,2,4,6-tetramethyl-l-piperidyl, and the like.

The alkylene radicals represented by Z in the generic formula can be illustratively 1,2-ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, l-methylethylene,

1 -methyl- 1,3 -propylene, Z-methyll ,3 -propylene, l-methyll ,4-butylene, l-methyl-1,5-pentylene, 3-methyll ,5 -penty1ene, l-methyl-1,6-hexylene, 1 -methyl- 1,7-heptylene, l-methyl-l ,8-octylene, l-methyll ,9-nonylene,

and the like.

Unsaturated alkylene radicals can be illustratively the divalent radicals derivable from the following unsaturated aliphatic hydrocarbons by removal of one hydrogen atom from each of two carbon atoms: 2-propene, 2-butyne, 2- butene, l-methyl-2-pentene, l-methyl-3-pentene, 2-methy1- 3-hexene, 2-methyl-4-heptene, 3-methyl-4-octene, l-methyl-4-octene, 4-nonene, S-decene, and the like.

Oxaalkylene and thiaalkylene radicals efer to alkylene radicals in which a carbon atom of the designated carbon chain is replaced with an oxygen atom or a sulfur atom, respectively, as for example, 3-oxapentarnethylene (CH CH -O-CH CH 3, thiapentamethylene (-CH CH -SCH CH and the like.

Acid addition salts of the bases represented by the above formula can be prepared by employing for example the following acids: hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, oxalic, tartaric, maleic, bendoic, succinic, and the like.

As examples of compounds which have the desired fungicidal activity and which can be successfully employed as fungicides in accordance with the process of this invention, there may be mentioned l3-diethylaminopropyl 3,4-dichlorobenzoate, a-rnethyl-fi-diet'hylaminobutyl 3,4-dichlorobenzoate, ,8- di-n-butylamino) propyl 3,4-dichlorobenzoate, y- 2,2,4,6-tetramethylpiperidino propyl 3,4-dichlorobenzoate, 'y- 2,6-dimethylpiperidino -propyl 3,4-dichlorobenzoate, 2-morpholinoethyl 2,5-dichlorobenzoate, v-morpholinopropyl 3,4-dichlorobenzoate, -(4-methylpiperidino propyl 3,4- dichlorobenzoate, 'y- (3 -methyl piperidino pro pyl 3 ,4-dichlorobenzoate, w-(2-methylpiperidino)-n-hexy1 3,4-dichlorobenzoate, [3-[fi-(Z-methylpiperidino) ethoxy]ethyl 3,4-dichlorobenzoate, ,8- fi- Z-methylpiperidino ethylmercapto ethyl 3 ,4-dichlorobenzoate, 'y-(2-methylpiperidino) propyl 3,5-dichlorobenzoate, -piperidinopropyl 3,4-dichlorobenzoate, 2-morpholinoethyl 3,4-dicl1lorobenzoate, S-dimethylaminoethyl 3,4-dichlorobenzoate, 'y-diethylaminopropyl 3,4-dichlorobenzoate, v-(di-n-butylamino) propyl 3,4-dichlorobenzoate,

3 'y-rnorpholinopropyl 3,4-dichlorobenzoate, v-(Z-methylpiperidino)propyl 3,4-dichlorobenzoate, 'ydiallylamino propyl 3 ,4-dichlorobenzoate, 'y- 2-methylpiperidino pro pyl 3-iodo-4-fiuorobenzoate hydrochloride, v-(Z-methylpiperidino) propyl 2,4-dichlorobenzoate, 4- Z-methylpiperidino -2-butynyl 3 ,4-dichlorobenzoate, 'y-(2-methylpiperidino) propyl 2,6-dichlorobenzoate, 'y-(Z-methylpiperidino)propyl 2,5-dich-lorobenzoate, 'y-morpholinopropyl 2,5-dichlorobenzoate, 4-(2-methylpiperidino)-2-butenyl 3,4-dichlorobenzoate, y- Z-methylpiperidino) pro pyl 3 ,4-dichlorobenzoate hydrochloride, w-(Z-methylpiperidino)-n-pentyl 3,4-dichlorobenzoate, and w-(Z-methylpiperidino)-n-decyl 3,4-dichlorobenzoate.

In carrying out the method of the present invention, compositions containing the active ingredient are applied to the infected or susceptible plant surfaces. A convenient and preferred method is to spray the plant surfaces with a liquid dispersion or emulsion of the toxicant.

The compositions of the present invention desirably contain in addition to the benzoate ester toxicant one or more of a plurality of additaments including water, hydroxylated carriers, petroleum distillates, and other dispersion media, surface-active dispersing agents, emulsifiers, and finely divided inert solids. The concentration of the benzoate ester compound in these compositions may vary depending on whether the composition is intended for direct application to plants or is designed as a concentrate. Those containing relatively high concentrations of the toXicant may be considered as concentrates and be subsequently diluted with additional inert carrier to produce the ultimate treating composition.

The compounds of the present invention are applied to plants in effective amounts, varying somewhat with the severity of the fungus infection and with other factors such as the environment in which treatment is conducted. In general, it will be found that an aqueous spray containing from about /8 to about 1 lb. of active material per 100 gallons of water is satisfactory when treatment is to be carried out in the greenhouse.

As is well understood in the art, a somewhat higher concentration of the fungicide is desirable when treatment is to be carried out in the field. In that case, the preferred range is from about /2 to about 2 lbs. of active ingredient in 100 gallons.

Treating compositions are most conveniently formulated by preparing liquid or solid concentrate compositions which are subsequently diluted to produce a composition of the desired concentration. Emulsifiable liquid concentrates may be prepared by incorporating from about to about 40 percent of the active ingredient and an emulsifying agent in a suitable water-immiscible organic liquid. Such concentrates may be further diluted with water to form spray mixtures in the form of oilin-water emulsions. Such spray compositions then comprise active toxicant, water-immiscible solvent, emulsifying agent, and water. Emulsifying agents are preferably blends of the non-ionic and ionic types and include condensation products of alkylene oxides with phenols and organic acids, polyoxyethylene derivatives of sorbitan esters, complex ether-alcohols, ionics of the aralkyl sulfonate type, and the like. Suitable organic liquids to be employed include aromatic hydrocarbons, aliphatic hydrocarbons, cycloaliphatic hydrocarbons, and mixtures thereof such as petroleum distillates.

Solid concentrate mixtures may be prepared by incorporating from about 5 to about 75 percent of the benzoate ester compound in finely divided solid carriers such as bentonite, Fullers earth, diatomaceous earth, bydrated silica, diatomaceous silica, talc, chalk, and the like. Such concentrates may be formulated, if desired, for direct use as dust treating compositions, or may be diluted, if desired, with additional inert solid carriers to produce dusting powders containing around 1 to 50 percent by weight of the benzoate ester toxicant. Alternatively, dispersing and/or wetting .agents may be incorporated along with the benzoate ester in the solid carrier to form wettable powder concentrates which subsequently may be dispersed in water or other aqueous carrier to form spray compositions. Suitable wetting and emulsifying agents include sodium lignosulfate, sulfonate-oxide condensate blends, sulfonate non-ionic blends, anionic wetting agents, and the like.

Further, the benzoate ester toxicant may be incorporated in solutions, simple dispersions, aerosol formulations and other media adaptable to be employed for treating vegetation.

In operating according to the method of the present invention, the toxicant composition is applied to infected or susceptible plant surfaces in any convenient fashion such as spraying, dusting, dipping, or drenching. A spray method is considered preferable, especially when large numbers of plants are involved, because of the rapidity and uniformity of treatment possible. In spraying, it is usually sufficient for the infected or susceptible surfaces to be thoroughly wet with the liquid dispersion employed. Good results have been obtained by employing spray compositions whether they be emulsions or aqueous dispersions of solid concentrates.

The following examples illustrate the invention but are not to be construed as limiting.

EXAMPLE 1 The evaluation of the effectiveness of compounds exemplified by the above formula against Phytophthora infestans, the causative organism of late blight of tomato, was accomplished in the greenhouse in the following manner.

Fungicidal compositions were prepared by dissolving 40 mg. of the compound to be tested in 1 ml. of a solution of cyclohexanone containing 55 mg. of sulfonate non-ionic blend (Toximul R and S, Stepan Chemical Company, Northfield, Illinois) and diluting to a volume of ml. with water. This composition then contained 400 ppm. of fungicide. To prepare a composition containing 1000 p.p.m., 100 mg. of the compound to be tested was dissolved in 1 ml. of the cyclohexanone-sulfonate non-ionic blend solution and then diluted to a volume of 100 ml. with water.

Four tomato seeds (Bonny Best variety) were planted in 4-inch plastic pots in sterilized soil and allowed to germinate, and the seedlings were thinned to two plants per pot. Twenty-eight days from the day of planting the test chemicals, compounded as described above, were sprayed on all leaf surfaces of the tomato plants and allowed to dry. A spore suspension of Phytophlhora injesmns was applied to the foliage with a sprayer, after which all plants were then placed in a moist chamber for 24 hours. At the end of this 24-hour period, the plants were returned to the greenhouse. After three days in the greenhouse, the plants were observed for development of the characteristic lesions or spots of late blight. The number of spots appearing on the treated plants was compared with the check plants and rated for the control of fungus achieved. The control rating scale used was as follows:

0no control lslight control 2m-oderate control 3-good control 4complete control, no fungus Chart 1 which follows sets forth the results of the testing of several benzoate esters against Phytophlhora infestans. In the chart, column 1 gives the name of the compound; column 2, the rate in terms of meg/ml. or p.p.m. which the compound was applied to the test plants; and column 3, the protection rating of the compound.

pment Protection Rating n S 6 d e 6 6 S Rm ma m n .mmrma m 432333311 29w wa 1 95 t w P w n m e Y w arm m P gmSrS em p CA a m u 6 m U MR .1 .sa h s e E mmi wwm per u .1 m WOADOOGOOG m w W O m ah W m w mln 4 fl 4 0 4 4 4 m a t u d 0 w m mm e n .wmm 1 ed 4 t 1 w wm rm m mwm Mnw mrxm wen c m mh rdmn n wme l I u .m rbrrb mn m m m I mm M m w m mm n r w m m n m m a y cw ham n m R m" m m lw pmm m w w t c n m t s A a a a w m mm m r M W fl t mr T6 1 4, r .w"wv. 3 a O S a O 6 O r I 3 3 0 h p l rf hf O 1 1 n al mon S 6 r r n O p r V. n y d "or d mfl w m od m d p. p .1 n n@ aa em m emm n m mew mdmnmf l f GtdVil u D. D mh 15 p W o n n d"D ewk m uwm v m m m. m 1 m fi r 10 d n .1 .1 t 2 i h l naO e o d dc h el e d 4L 16L O 1 .l t t% h a o R. 1 1 m n 1 o a ar me im "h mnmaa n t n a d h a m p w e .m mm mm m "anummmm .mmo fiw m M D: Dh r .m mm n t e .w o a n n w o e we he a new m ym a f d S f l w 8 h m t t lh t mO wl .mfi e n e Pt e, s T m aw a m am m wmnm t 1 1 1 m Wmrmnmmm mm mm mm mmr m m mmmomw hm em om mm mmm eom t SttshPtUm r w 0 5 0 5 5 I f S mg 332232221121 L mm .m 0 w H mm um w w mdmwume m U .D e uc .OR f .l Oar 1 r. I y a 6 Pet e r P w a a.m m mw v m nmto s mo omwmmmm w o0 n m m amt 4 04 4 na m V P w W .m L OE I m 1R .1.L d e0nv y D. 90 M e t w m ec m wsm nm fl V6 p o t n n wn s 2.1m. m W wo m l t 1 p HAW. rK 0 E ya t T m m m 1 u L n 6 k R m m m m? P wo a w mm A m m n .02, M y w tm m a H n 4 ed mum. P s n m w o mm l A mt, e 3 3 1 P K 0 e S .IV.A w .m On (pdm mw u r. 1 a w w. mm an Eli/mam symmwam m m mm m p nmu nm hfma dm 0 )1 .H .0 m Sy p w le p 0 0M m m 6m. dr m S pV m m .m v n h o g o d m h m m m HC &0 o n no Wu em m otd mm a e m U mom o. p S m a W y a h a my .w wam m wdrm w n p D. .l I. we mm M nn dam ow p .mmem n a a wma M m c a m m d w h a m i t t V. 10 1 mm mm ay? Ammm m w H mm m p m m a m m m a n md c MOd 2 12 S a 6 O G a D D T(.\.D J\3(.\ f X 1 r S l v a v v r to E PtfatP gicidal compositions yces phaseoli var.

pared with the check gus recorded.

g system as in Example Application Rate, meg/ml.

EXAMPLE 4 The compounds of the present invention were tested against Uromyce Example 1. 1

re planted in 4-inch clay pots and ants per pot. On the tenth day the leaf surfaces and allowed CHART 4 s plzaseoli var. typica, causative organism Three bean seeds we later thinned to two pl typica was applied to the foliage with a sprayer. All the plants were immediately placed in the moist chamber for and ratings of the control of the fun Compound 24 hours and then returned to the greenhouse. On the twentieth day the plants were observed for develo of the disease, the treated plants corn plants The results, using the same ratin of bean rust. Formulation of the fun Was done as described in test chemical was sprayed on all to dry. A spore suspension of Urom 1, are given in Chart 4 4&L33214um43342442 Protection Rating placed above h they were removed.

plants were obn The appearance that of the check fungus were ree as for Ex- A r tio R ge, meg/ml.

ildew were ic al days the CHART 2 Compound benzoate.

-(2-methy1piperidino) propyl 3,4'dichlorobenzoate hydrochloride.

-(2-methylpiperidino)propyl 2,5-dichlorobenzoate. (Z-methyIpiperidino)propyl 3-iodo-4- fluorobenzoate hydrochloride.

iporidino) propyl 2,4-dichlorobenzoate.

' -(Z-methylpiporidino)propyl 2,6-dichlo1'obonzoate.

heavily infested with powdery m them for about five days, after wh At the end of five addition served for development of the disease.

of the treated plants was compared with plants and ratings of the control of the corded. The control rating scale is the sam ample 1. Results are set forth in Chart 2.

'y-(Z-methyIpiperidinO)propyl3,4-dichloro- -(2-methylp no)propy1 2,6-diylamiuoethyl 3,4-dipiperidino) chlorobcnzoata fi-Dimethylaniino benzoate a-Meth chlorobenzoate or-Methyl-rS-dicth ehlorobenzoate Besides the greenhouse evaluations described abov testing of y-(2-methylpiperidino)propyl 3,4-dichlorobenzoate was carried out in the field against certain organisms T (2-methyl (4-methylpiperidino) propyl 3,4-dichloro benzoateis. s r i w-(2-methy1piperidino)-n-decyl 3,4-dichlorobenzoate. r

EXAMPLE 7 The compounds of the present invention were tested against Colletotrichum lagenarium, the causative organism of cucumber anthracnose. Formulation of the fungicides Four cucumber seeds (Green Prolific variety) were planted in sterilized soil in 4-inch plastic pots, and after 7 was done as described in Example 1.

which damage crop plants and others which severely injure ornamental plants.

A 25 percent wettable powder composition was prepared by mixing 25 parts by weight of 'y-(2-methylpiperidino)propyl 3,4 dichlorobenzoate, 63 parts by weight of diatomaceous silica, 10 parts by weight of ultrafine hydrated silica, and 1 part each by weight of highly purified sodium lignosulfate and an anionic wetting agent (Nopco anionic wetting agent, Nopco Chemical Co., Newark, N.J.). When 181.7 g. of this 25 percent wettable powder was placed in 10 gallons of water, the equivalent of 1 lb. of active material per 100 gallons of water was obtained. 7

In addition, an emulsifiable concentrate was prepared by mixing 30 parts of v-(Z-methylpiperidino)propyl 3,4- dichlorobenzoate, 62 parts of heavy aromatic naphtha, parts aromatic sulfonate-oxide condensate blend, and 3 parts sulfonate non-ionic blend. These proportions provide a dilution ratio such that 150 ml. of the concentrate brought up to 10 gallons with Water gave an emulsion of 1200 p.p.m. of fungicidal agent.

EXAMPLE 5 The ability of v-(Z-methylpiperidino)propyl 3,4-dichlorobenzoate to combat Venturia inaequalis, the causative organism of apple scab, was tested.

A percent wettable powder composition of 'y-(2- methylpiperidino)propyl 3,4-dichlorobenzoate was used at dosages of 0.5 and 1 lb. of active material per 100 gallons of Water in the treatment of Venturia inaequalis.

A block of 56 four-year-old apple trees of the McIntosh variety was used, randomization of treatments being accomplished by employing a modified Latin square design. Each treatment was applied to eight trees. A standard orchard sprayer specially modified to spray small volumes of spray materials was used with a three-nozzle orchard boom to apply the materials.

All treatments were properly Weighed, added to a small volume of water, thoroughly mixed, and brought to a final volume of 10 gallons of water. Each tree was then sprayed at a pressure of 250 p.s.i. until run-off. Applications were made May 9, 15, 22, 29; June 6, 12, 19, 26; July 2, 10, 17, 24, and 31.

Each tree of every treatment was observed for foliar lesions caused by the apple scab fungus. Ten terminals (branches) were selected at random on each tree and the percentage of leaves with apple scap lesions was determined for each terminal.

Results of the treatment are shown in Chart 5. Column 1 gives the name of the compound; column 2, the rate of application in terms of pounds per 100 gallons of mixture; and columns 3, 4, 5, and 6, the percent of foliage on 80 terminals with apple scab lesions on the dates evaluated.

A field trial was run to determine the efficacy of 'y-(2- methylpiperidino)propyl 3,4 dichlorobenzoate against 8 Erysiphe cichoracearum, the causal organism of powdery mildew on cantaloupe.

The fungicidal compound formulated as a 25 percent wettable powder, supra, was used at dosages of 0.5 and 1 lb. of active material per gallons of water.

In addition, the fungicidal compound, formulated as an emulsifiable concentrate, supra, was used at a dosage of I 0.5 lbnof active material per 100 gallons of water.

A four block experimental design was employed, each block measuring 36 feet by 78 feet and containing fourteen rows seeded with the Harvest Queen variety of cantaloupe. Each treatment was applied to one row in every block using a specially constructed high clearance row-crop sprayer equipped with six nozzles.

All treatments were properly weighed or measured and thoroughly mixed with 10 gallons of water, and the plants were sprayed at a pressure of 200 psi. until run-off. Applications of the fungicide were made June 22, 27; July 5, 11, 18, 25; August 2, 7, 14, 21, 28; and September 5 and 12.

To evaluate the incidence of disease, two hundred leaves were selected at random on each row of every treatment and the percentage of the counted leaves with signs or symptoms of the casual agent determined.

The effectiveness of 'y-(2-methylpiperidino)propyl 3,4- dichlorobenzoate in combatting Erysiphc cichoracearum is shown in Chart 6. Column 1 gives the name of the compound; column 2, the rate of application in terms of pounds per 100 gallons of mixture; and columns 3 and 4, the percent of leaves with signs or symptoms of the casual agent on the dates determined.

CHART 6 Percent Foliage Application Rate, 110.} 100 gal.

Compound Diseased Control 7-(2-methylpiperidino)propyl 3,4-

dkgilorobenzoate DJ 9. HMOQ es WP=wettable powder; EC =emulsifiable concentrate.

EXAMPLE 7 In a further field trial, the efiicacy of 'y-(2-rnethylpiperidino)propyl 3,4-dichlorobenzoate in controlling Sp/zaerotheca pannosa var. rosae, the casual organism of powdery mildew of rose, was examined.

The fungicide was formulated as a 25 percent wettable powder and as an emulsifiable concentrate, both previously described.

A total of 300 roses, 100 each of the Poinsettia, Peace, and Crimson Glory varieties, were used in this experiment. All roses were planted on six-foot centers in 20 rows, each row containing 15 bushes, five of each variety.

All treatment were properly weighed or measured and thoroughly mixed with five gallons of water. Each bush was sprayed at a pressure of 250 psi. until run-oil? using a specially constructed high clearance row-crop sprayer equipped with six nozzles. Applications were made June 7, 14, 21, 28; July 5, 12, 18, 24; and August 1.

Each rose bush of every treatment was evaluated by two observers for the percent foliage diseased by S. pannosa var. rosae, and the results appear in Chart 7 which follows. Column 1 lists the compound used; column 2, the rate of application; and columns 3 through 9, the percent rose foliage with powdery mildew of each variety of rose on the dates evaluated.

CHART 7 Poinsettia Peace Crimson Glory Application Compound i 8gal 7/11 7/24 8/1 7/11 7/24 8/1 7/11 7/24 8/1 Control 59.5 84.0 09.0 40.0 7.5 4.0 6.0 7.5 18.5 -(2-methylpipcridino)propyl 3,4- lWP -1 1.6 1.2 1.8 1.6 1.0 1.6 1.6 1.0 1.6

dichlorobenzoate.

Do 0.5130 2.0 4.0 3.0 0.0 1.2 0.8 1.0 1.0 1.8 Do IEC 4.0 5.0 3.5 1.0 1.0 1.0 1.0 1.0 2,0

WP=wettable powder; EC =e1nulsifiable concentrate.

EXAMPLE 3 CHART 9 An evaluation of the fungicidal effectiveness of v-(2- methylpiperidino)propyl 3,4 dichlorobenzoate against Pei-centFoliage Diseased Microsphaera alni, var. vaccinii, casual organism of poW- Application dery mildew Of catalpa, was made. Compound 1b fiateal ggglgy Leaf Spot The fungicide was formulated as an emulsifiable concentrate, as previously described, and used at a dosage 9/13 9/21 9/13 9/21 of 1 lb. of active material per 100 gallons of water.

A total of twenty-four catalpa trees were used in this Control 0 603 7 17.8 223 experiment. An orchard sprayer, specially modified to 2.1m85555555555555; {1561:1111 1.0 0.4 0.4 3.8 spray small volumes of spray materials, was used with a 3,4flich10r0benz0atethree-nozzle orchard boom to spray at a pressure of 250 p.s.i. until run-off. Applications of the fungicidal mixture Ec=emulsifiab1e were made on July 12, 19, 26; August 1, 9, 14, 21, 28; EXAMPLE 10 September 6 apd A stud was made to determine the ability of 'y-(2- The eYaluanon of the Incidence of disease was done 30 methylpip eridinwpropyl 3 4-dichlorobenzoate to control by selecting one hundred leaves at random on each tree Microsphaem Causal organism of powdery mildew receiving treatment, and determining the percentage of of lilac the counted leaves with .signs or Symptoms the Casual The fun icide was formulated as an emulsifiable conagent' The .results of thls evaluation appear 1n chart centrate at a dosage of 1 lb. of active ingredient per 100 Column 1 lists the name of the compound used; column gallons of Water The material was applied using a Sprayer the rate i ap p canon} and columns. and the specially modified to spray small volumes of spray matepercent cata pa foliage wlth powdery mlldew' rials, and each of the twenty lilac bushes used in the test CHART 8 was sprayed to run-off. Applications were made on July 13, 19, 26; August 1, 8, 14, 22, 28; September 5 and 11. Percent Ca'mpa Fohme 40 Each lilac bush was evaluated for the percent foliage Application with Powdery m with signs or symptoms of M. alni. The results are listed 1b $35 at in Chart 10. Column 1 lists the name of the compound g 8/22 9/0 9/18 tested; column 2, the rate of application; and columns 3 and 4, the percent foliage diseased on the date evaluated. fiiiiftiaiiiii siiaiiaidtisii" iis'oIIIIIII 3:3 5:3 5:3 CHART 3,4-dichlorobenzoate.

t Percent Foliage EO=e1nulsiIiable concentrate. Compound i a??? f i EXAMPLE 9 5O 9/15 9/18 The fungicidal activity of -(Z-methylpiperidino)propyl 1 4 4 62 6 3,4dichlorobenzoate against Erysiphe cichoracearum, S2 ixffg g ggfiaihgfifgh571 3:61:11: 1 1 which causes zinnia powdery mildew, and against Cercos- 3,4410111010136111081 para zinniae, which causes Cercospora leafspot of Zinnia, was tested 5 5 EC=en1ulsifiable concentrate.

The fungicide Was formulated as an emulsifiable con- The Compounds of h present i tio an readily be centrate, as described above, and used at a dosage of 1 ptepatgd in the f ll i manner of active material per 100 gallons of water. Applica- A Solution of an appropriate alkylaminoalkanol in Was done 115mg 3 tspeciallytconfimcted chloroform is prepared and to it is added a chloroform p p y q p With SIX nozzles, and Plants solution of an appropriate substituted benzoyl chloride, were spayed to followed by refluxing for about 3-4 hours.

In thls expenment two blocks each 20 feet by 36 The reaction mixture is concentrated in vacuo on the feet, were used, each block containing six double planted Stcam bath and the residue, chhtaihing the crude alkyh rows of the State Fair variety of Zinnia. Every treatment amihoalkyl henmate eSter hydrochloride is dissolved in was replicated in each block- Applications were made July 65 water. The aqueous solution is made basic with aqueous 13, 20, August and September 6 sodium hydroxide or potassium hydroxide solution and and the freed organic base is extracted with ether. The ether The results were determined as follows Twenty-five solution is washed with water, dried, and distilled to yield terminals of plants in each treatment row were evaluated h desired f i id l compouhd for Percentage of leaves P terminal With Signs Of Y P- The following will serve to illustrate the preparation. toms of E. cichoracearum or C. zimziae, and the results t I are shown in Chart 9. Column 1 lists the name of the I' 'Yi(2mlefhylplpmdl'w) compound; column 2, rate of application; and columns p'opyl 34'dwhlombenzoate 3, 4, 5, and 6, the percent of foliage diseased on the date A solution of 156.2 g. (1 mole) of -(2-methylpiperievaluated. dino)propyl alcohol in 900 ml. chloroform was prepared 1 1 and 150 ml. (2 moles) of thionyl chloride were added at a rate promoting gentle refluxing. When addition was complete, the mixture was refluxed for 3 hours.

The reaction mixture was evaporated to dryness in vacuo on the steam bath and the residue recrystallized from boiling ethyl alcohol to yield 176 g. (83 percent) of 'y-(Z-rnethylpiperidino)propyl chloride hydrochloride having a melting point of about 170174.5 C.

The material thus obtained was dissolved in water and the solution basified with potassium hydroxide, thus liberating the free base, 'y-(2-methylpiperidino) propyl chloride, which was extracted with ether. The ether solution was washed with water, dried over magnesium sulfate, and concentrated in vacuo on the steam bath to yield 125.5 g. of purified 'y-(2-rnethylpiperidino)propyl chloride.

A mixture of 137.5 g. (0.72 mole) of 3,4-dichlorobenzoic acid and 125.5 g. (0.72 mole) of'y-(Z-methylpiperidino)propyl chloride in 850 ml. of isopropyl alcohol was refluxed for 24 hours. After cooling, the reaction mixture was filtered and the solid product washed with ether. In this manner, 181.0 g. of 'y-(2-methylpiperidino)propyl 3,4-dichlorobenzoate hydrochloride was obtained. A sample recrystallized from ethyl alcohol had a melting point of about 172-174 C.

Analysis.-Calc.: N, 3.82; Cl, 29.01. Found: N, 3.88; Cl, 29.70.

The above hydrochloride Was dissolved in water and the free base liberated by adding 0.55 mole of 50 percent sodium hydroxide solution. The free base was extracted with ether and the ether solution washed with water and dried and distilled to give 120 g. of v-(Z-methylpiperidino) propyl 3,4-dichlorobenzoate having a boiling point of about 156-157 C. at 0.20 mm; n =1.53441.5345.

AnalysiS.-Calc.: C, 58.19; H, 6.40; N, 4.24. Found: C, 59.57; H, 6.51; N, 4.07.

The same compound can be prepared by the following alternative method.

Preparation 2.'y-(Z-methylpiperidino) propyl 3,4-dichlr0benz0ate A solution of 312.4 g. (2.0 moles) of -(2-methylpiperidino)propyl alcohol in 2 liters of chloroform was prepared and to the solution was added a solution of 418.8

, g. (2.0 moles) of 3,4-dichlorobenzoyl chloride in 500 ml.

of chloroform. After the addition was complete, the mixture was refluxed for 3 hours.

The reaction mixture was evaporated to dryness in vacuo on the steam bath and the residue, 'y-(2-methylpiperidino) propyl 3,4-dichlorobenzoate hydrochloride, was dissolved in water. The solution was made basic by adding 133.2 g. (2.2 moles) of cold aqueous potassium hydroxide solution and the liberated base was extracted with ether. The ether solution was dried and distilled. A total of 492.7 g. (75 percent) of 'y-(Z-methylpiperidino)propyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 160-166 C./0.3 mm.

The following is an additional modification of the above procedure.

Preparation 3.'y-(2-methylpiperidino) propyl 3,4-dichlorobenz0ate A solution of 156 g. (1.0 mole) of -(2-methylpiperidino)propyl alcohol in one liter of chloroform was heated to refluxing and a solution of 210 gm. (1.0 mole) of 3,4- dichlorobenzoyl chloride in 250 ml. of chloroform was added slowly via a dropping funnel. When the addition was complete, the reaction mixture was refluxed for 3 hours, after which one liter of chloroform was distilled ofl. To the warm (temp. 50-60 C.) remaining solution were added'2 liters of hexane. The mixture was refluxed for 30 minutes and cooled to 10 C. The solid, crude 'y-(2-methylpiperidino)propyl 3,4-dichlorobenzoate hydro. chloride precipitated thereby was recovered by filtering on a Buechner funnel. The solid product was washed several times with hexane. Next the solid, crystalline product was slurried with hexane then filtered and washed with ether 12 to remove unwanted starting material, impurities, and the like.

The amino ester hydrochloride thus obtained was suspended in a mixture of one liter of ether and two liters of water. The mixture was basified in the cold by adding gm. of 50 percent aqueous sodium hydroxide solution. The ether solution of the free base, 'y-(l-methylpiperidino)propyl 3,4-dichlorobenzoate, was separated and the basic, aqueous layer discarded. The ether solution was washed free of chloride ions with de-ionized water and dried first over sodium sulfate, then over magnesium sulfate. After filtering, the drying agent was washed with ether and the total ether solution concentrated to dryness to yield 261 g. of the desired product (79 percent).

Preparation 4.-ot-Methyl-B-dimethylaminoet/zyl 3,4-dichI0r0benz0ate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and a-rnethyl-{i-dimethylaminoethanol as the reactants, a-methyl-B-dimethylaminoethyl 3,4- dichlorobenzoate was obtained as a liquid having a boiling point of about 114-ll7.5 C./0.35 mm.; n =l.5218-1.5220.

Analysis.--Calc.: C, 52.19; H, 5.48; N, 5.07 Found: C, 52.17; H, 5.44; N, 5.00.

Preparation 5.-B-Dimethylaminoethyl 3,4-dichl0robenz0ate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and fl-dimethylaminoethanol as the reactants, fi-dimethylaminoethyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about -121 C./O.26 mm.; n =1.53201.5322.

Analysis.Calc.: C, 50.42; H, 5.00; N, 5.34. Found: C. 50.17; H, 5.08; N, 5.24.

Preparation 6.,B-(Diethylamin0) propyl 3'4-dichlorobenzoate Preparation 7.a-methyl-fi-dicthylaminobutyl 3,4-dichl0r0benz0ate Found:

Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and 1-methyl-4-diethy.laminobutyl alcohol as reactants, a-methyl-B-diethylaminobutyl 3,4 dichlorobenzoate was obtained as a liquid having a boiling point of about -159 C./0.45 mrn.; 11 l.51211.5130.

Analysis.Calc.: C, 57.83; H, 6.98; N, 4.22. Found: C, 57.63; H, 6.88; N, 4.16.

Preparation 8.fi-(Di-n-bulylamina) propyl 3,4-dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and fi-(di-n-butylamino) propyl alcohol as the reactants, p-(di-n-butylamino) propyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 162.5-166" C./0.30 mm; 1.50721.5075.

Anaylsis.Calc.: C, 60.00; H, 7.55; N, 3.89. C, 60.11; H, 7.56; N, 3.69.

Preparation 9.'y-(Diethylamino) propyl 3,4-dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and 'y-(diethylamino)propyl alcohol as the reactants, 'y-(diethylamino)propyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 140.5145.5 C./0.l3 mm; n =l.5l95- 1.5197.

Found:

13 Anaylsis.-Calc.: C, 55.27; H, 6.29; N, 4.61. Found: C, 54.98; H, 6.44; N, 4.35.

Preparation 1 0.-'y- (Di-n-bnty lam ino) propyl 3,4-dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and 'y-(di-n-butylamino propyl alcohol as reactants, 'y-(di-n-butylamino)propyl 3,4- dichlorobenzoate was obtained as a liquid having a boiling point of about 163.5 C./0.25 mm; n =1.5O87.

Analysis.Calc.: C, 60.00; H, 7.55; N, 3.89. Found: C, 59.80; H, 7.61; N, 3.63.

Preparation ]1.'y-Morph0linopropyl 3,4-dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoy1 chloride and 'y-morpholinopropyl alcohol as reactants, v-rnorpholinopropyl 3,4-dichlorobenzoate was obtained which was purified as the hydrochloride having a melting point of about 199200 C.

Analysis.--Calc.: C, 47.40; H, 5.11; N, 3.95 Found: C, 47.46; H, 5.02; N, 3.77.

Preparation 12.-'y- (Z-methylpiperidino propyl 2,4- dichlorobenzoate Following the procedure of Preparation 2 and using 2,4-dich1orobenzoyl chloride and v-(Z-methylpiperidino) propyl alcohol as the reactants, "y-(Z-IHCthYIPiPGIidlHO) propyl 2,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 144148 C./0.06 rnrr1.; n =1.53541.5358.

Analysi.r.-Calc.: C, 58.19; H, 6.41; N, 4.24. Found: C, 57.99; H, 6.44; N, 4.13.

Preparation .73.-'y-(Z-methylpiperidino) propyl 2,6- a'iehlorobenzoate Following the procedure of Preparation 2 and using 2,6-dichlorobenzoyl chloride and 'y-(2-methylpiperidino) propyl alcohol as the reactants, y-(Z-methylpiperidino) propyl 2,6-dichlorobenzoate was obtained as a liquid having a boiling point of about 142-144 C./0.07 mm; n =1.5270.

Analysis.-Calc.: C, 58.19; H, 6.40; N, 4.24. Found: C, 57.96; H, 6.54; N, 4.16.

Preparation 14. (Z-methylpiperidino propyl 2,5

dich lorobenzoate Preparation 15.-'y-Morpholinopr0pyl 2,5-dichlor benzoa te Following the procedure of Preparation 2 and using 2,5-dichlorobenzoyl chloride and 'y-rnorpholinopropyl alcohol as the reactants, rnorpholinopropyl 2,5-dichlorobenzoate was obtained as a liquid having a boiling point of about ISO-156 C./0.24 mm.; n =1.5408-1.5412.

Analysis.Calc.: C, 52.84; H, 5.38; N, 4.40. Found: C, 52.81; H, 5.49; N, 4.37.

Preparation I6.-B-Morpholinoethyl 2,5-dicltlor0- benzoate Following the procedure of Preparation 2 and using 2,5-dichlorobenzoyl chloride and 2-morpholinoethyl alcohol as the reactants, fi-morpholinoethyl 2,5-dichloroben' zoate was obtained as a liquid having a boiling point of about 149-150 C./0.17 mm.; n =1.546O.

Analysis.-Calc.: C, 51.33; H, 4.97; N, 4.60. Found: C, 51.31; H, 4.85; N, 4.76.

l 4 Preparation 17.-[.?-Morph0lin0ethyl 3,4-dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and 2-morpholinoethy1 alcohol as the reactants, omorpholinoethyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 151154 C./0.15 rnrn.

Analysis.-Calc.: C, 51.33; H, 4.97; N, 4.60. Found: C, 51.57; H, 4.83; N, 4.59.

Preparation I8.'y-(3-methylpiperidino)propyl 3,4- dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and v-(3-methylpiperidino) propyl alcohol as reactants, 'y-(3-methylpiperidino)propyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 162 C./0.10 rnrn.; n =1.5322.

AnaIysis.-Calc.: C, 58.19; H, 6.40; N, 4.24. Found: C, 58.25; H, 6.13; N, 4.44.

Preparation 19.-'y- (4-methylpiperitlin0 )propyl 3,4- dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and 'y-(4-methy1piperi-dino) propyl alcohol .as reactants, 'y-(4-rnethylpiperidino)propyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 163164 C./0.11 IHITL; n =1.5311.

Analysis.-Calc.: C, 58.19; H, 6.40; N, 4.24. Found: C, 57.67; H, 6.45; N, 4.22.

Preparation 20.w- (Z-methylpiperia'ino) -n-hexyl 3,4- dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and w-(2-methylpiperidino)- n-hexanol as reactants, w-(2-n1ethylpiperidino)-n-hexy1 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 166-167 C./0.02 nun; n =1.5268.

Analysis.-Calc.: C, 61.29; H, 7.30; N, 3.76. Found: C, 61.17; H, 7.42; N, 3.62.

Preparation 21.-'y-(2,2,4,6-tetramethylpiperidino)propyl 3,4-dichl0r0benz0ate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and -(2,2,4,6-tetramethylpiperidino)propyl alcohol as reactants, -(2,2,4,6-tetran1ethylpiperidino)propyl 3,4-dichlorobenzoate was obtained as a liquid having a boilinng point of about 154- 159 C./0.015 mm.

Analysia-Calo: C, 61.29; H, 7.30; N. 3.76. Found: C, 61.22; H, 7.26; N, 3.68.

Preparation 22.y-(2,6-dimethylpiperidino)propyl 3,4- dichlorobenzoate Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and -(2,6-dimethylpiperidino)propyl alcohol as reactants, 'y-(2,6-dirnethylpiperidino)propyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 158-162 C./0.025 mm.; n =1.5348.

Analysis.-Ca1c.: C, 59.30; H, 6.73; N, 4.07. Found: C, 58.52; H, 6.56; N, 4.06.

Preparation 23.'y- (Z-methylpiperidino propyl 3,5- dichlorobenzoate Following the procedure of Preparation 2 and using 3,5-dichlorobenzoyl chloride and -(2-methylpiperidino) propyl alcohol as reactants, v-(2-methylpiperidino)propyl 3,5-dichlorobenzoate was obtained .as a liquid having a boiling point of about 166-168 C./0.22 mm; n =1.53lO.

Analysis.-Calc.: C, 58.19; H, 6.40; N, 4.24. Found: C, 58.15; H, 6.54; N, 4.32.

1 Preparation 24.--'y-(Z-methylpiperidino)-2-butenyl 3,4- dichlorobenzoate Following the general procedure of F. F. Blicke and J. H. Biel, J. Am. Chem. Soc., 79, 5508 (1957), a mixture of 75.8 g. (0.715 mole) of 1-hydroxy-2-chloro-3-butene and 228 g. (2.3 moles) of ot-pipecoline was heated on the steam bath for an hour. The precipitated u-pipecoline hydrochloride was filtered off and the filtrate distilled to yield 4-(2-methylpiperidino)-2-butene-1-01 having a boiling point of about 86.587 C./0.13 mm.; n =1.4978.

Analysis-Cale: C, 70.95; H, 11.31; N, 8.27. Found: C, 71.09; H, 11.43; N, 8.49.

Following the procedure of Preparation 2 and using 3,4-dichlorobenzoyl chloride and 4-(2-methylpiperidino)- 2-butene-1-ol as reactants, 'y-(2-methylpiperidino)-2-butenyl 3,4-dichlorobenzoate was obtained as a liquid having a boiling point of about 166167.5 C./0.1 mm.; "D251: 1.5451.

Analysis-Cale: C, 59.65; H, 6.18; N, 4.09. Found: C, 59.58; H, 6.35; N, 3.94.

I claim:

1. A method for protecting plants from attack by fungi which comprises contacting a fungus-susceptible plant with a fungicidal amount of a substance selected from the group consisting of a compound having the following formula and the acid-addition salts thereof 2 wherein R and R are halogen; R and R when taken separately are selected from the group consisting of C -C alkyl and C -C alkenyl', R and R when taken together with the nitrogen atom to which they are attached, represent a radical selected from the group consisting of morpholino, C.,C polymethyleneimino, and lower-alkyl substituted C -C polymethyleneimino; and Z is selected from the group consisting of C -C saturated alkylene, C -C unsaturated alkylene, 0 -0 oxaalkylene, and C C thiaalkylene.

Z. The method of claim 1 wherein said substance is applied in combination with an inert diluent.

3. The method of claim 1 wherein said substance is applied in combination with an inert diluent and a wetting agent.

4. The method of claim 1 wherein said substance is applied in a composition containing within the range of about /s to about 2 lb. of fungicidally-active material per 100 gallons of water.

5. The method of claim 1 wherein y-(Z-methylpiperidino)propyl 3,4-dichlorobenzoate is the fungicidallyactive substance.

6. The method of claim 1 wherein 'y-(Z-methyIpiperidino)propyl 3,4-dichlorobenzoate hydrochloride is the fungicidally-active substance.

7. The method of claim 1 wherein -(2-methylpiperi- 16 dino)propyl 2,6-dichlorobenzoate is the fungicidallyactive substance.

8. The method of claim 1 wherein fi-diethylaminopropyl 3,4-dichlorobenzoate is the fungicidally-active substance.

9. The method of claim 1 wherein -(2,6-dimethylpiperidino propyl 3,4-dichlorobenz-oate is the fungicidallyactive substance.

10. A liquid concentrate, suitable for dilution with water to yield a fungicidal spray, said concentrate comprising an inert solid diluent and a wetting agent in admixture with an amount within the range from about 5 to about 40 percent by weight of a fungicidal substance selected from the group consisting of a compound having the following formula and the acid-addition salts thereof:

wherein R and R are halogen; R and R when taken separately are selected from the group consisting of C C alkyl and C -C alkenyl; R and R when taken together with the nitrogen atom to which they are attached, represent a radical selected from the group consisting of morpholino, C -C polymethyleneimino, and lower-alkyl substituted C -C polymethyleneimino; and Z is selected from the group consisting of C -C saturated alkylene, c c oxaalkylene, and G 0 thiaalkylene.

11. A fungicidal composition comprising an inert solid diluent, a wetting agent, and a fungicidal proportion of a substance selected from the group of a compound having the following formula and the acid-addition salts thereof:

wherein R and R are halogen; R and R when taken separately are selected from the group consisting of C -C alkyl and C -C alkenyl; R and R when taken together with the nitrogen atom to which they are attached, represent a radical selected from the group consisting of morpholino, C -C polymethyleneimino, and lower-alkyl substituted C -C polymethyleneimino; and Z is selected from the group consisting of C r-C saturated alkylene, C -C unsaturated alkylene, C -C oxaalkylene, and C -C thiaalkylene.

References Cited UNITED STATES PATENTS 2,358,925 9/1944 Haller et al. l67-33 2,454,061 l1/1948 Hill et al. 167-30 3,025,297 3/1962 Robinson 260294.3 3,175,941 3/1965 Dekker 167-30 ALBERT T. MEYERS, Primary Examiner.

GEORGE A. MENTIS, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No 3 ,322 ,618 May 30 1967 Harold M. Taylor It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column l, lines 46 to 49 the formula should appear as shown below instead of as in the patent O R R CO-Z-N\ R 4 same column 1 line 55 for "C -C read (I -C column 2 line 44 for "bendoic" read benzoic column 7 line 66 for "(Z-methylpiperidino)" read y-(Z-methylpiperidino) column 13 line 6 for "y- (di-n-butylamino pro-" read y-[di-n-butylamino)pro- Signed and sealed this 25th day of June 1968 (SEAL) Attest:

EDWARD M.FLETCHER,JR. EDWARD J. BRENNER Attesting Officer Commissioner of Patents 

